Methylmalonic aciduria: metabolic block localization and vitamin B 12 dependency.
Methylmalonic aciduria is an inborn error of metabolism characterized by neonatal or infantile ketoacidosis. Leukocytes isolated from the peripheral blood of a 1-year-old child with this disorder converted negligible quantities of propionate-3-C(14) to carbon dioxide, but oxidized succinate-1,4-C(14) normally, an indication of a block in the conversion of propionate to succinate. Parenteral administration of vitamin B(18) resulted in a reduction in methylmalonic acid excretion and an increase in propionate oxidation by leukocytes in vitro. The results suggest a mutation of methylmalonyl-CoA isomerase, a vitamin B(12), dependent enzyme which converts methylmalonyl-CoA to succinyl-CoA, and provide the first demonstration of vitamin B(12) "dependency" in man.
D000138:Acidosis / Q000097:blood*; D000592:Amino Acid Metabolism, Inborn Errors / Q000652:urine; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes; D003065:Coenzyme A; D006801:Humans; D006836:Hydro-Lyases; D007223:Infant; D007535:Isomerases / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D008314:Malonates / Q000652:urine*; D008661:Metabolism, Inborn Errors / Q000097:blood*; D008967:Molecular Biology; D009154:Mutation; D011422:Propionates / Q000378:metabolism*; D011732:Pyridoxal Phosphate / Q000378:metabolism; D013386:Succinates / Q000378:metabolism*; D014805:Vitamin B 12 / Q000378:metabolism*; D014977:Xanthurenates / Q000652:urine
D002247:Carbon Isotopes; D008314:Malonates; D011422:Propionates; D013386:Succinates; D014977:Xanthurenates; D002245:Carbon Dioxide; D011732:Pyridoxal Phosphate; D006836:Hydro-Lyases; D007535:Isomerases; D014805:Vitamin B 12; D003065:Coenzyme A